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RORγt+Foxp3+ regulatory T cells in the regulation of autoimmune arthritis
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  • Kotona Furuyama,
  • Yuya Kondo,
  • Masaru Shimizu,
  • Masahiro Yokosawa,
  • Seiji Segawa,
  • Akira Iizuka,
  • Reona Tanimura,
  • Hiroto Tsuboi,
  • Isao Matsumoto,
  • T Sumida
Kotona Furuyama
University of Tsukuba
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Yuya Kondo
University of Tsukuba
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Masaru Shimizu
University of Tsukuba
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Masahiro Yokosawa
University of Tsukuba
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Seiji Segawa
University of Tsukuba
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Akira Iizuka
University of Tsukuba
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Reona Tanimura
University of Tsukuba
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Hiroto Tsuboi
University of Tsukuba
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Isao Matsumoto
University of Tsukuba
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T Sumida
University of Tsukuba
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Abstract

RORγt+Foxp3+ regulatory T (Treg) cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset of Treg cells, which have the potential to regulate the development of experimental autoimmune encephalomyelitis (EAE) thorough a specific repression of T helper 17 (Th17) cell mediated inflammation. However, the function of Tr17 cells the development of other autoimmune diseases such as autoimmune arthritis remains unclear. Collagen induced arthritis (CIA) was found to be prolonged in Foxp3creRORγtfl/fl mice, in which Tr17 cells were deleted, compared with Foxp3wtRORγtfl/fl mice. Tr17 cells were significantly increased in ankle joints compared with draining lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6) was up-regulated on Tr17 cells compared to RORγt negative Treg cells. CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS) expression was also up-regulated on Tr17 cells compared to RORγt negative Treg cells. IL-10-producing cells and Blimp-1+ cells were increased in Tr17 cells compared to RORγt-Treg cells. Tr17-enriched Treg cells significantly suppressed proliferation of conventional T cells compared with CCR6-Treg cells. Tr17 cells increased during the clinical course of CIA and accumulated in inflamed joints. These cells expressed CD25, CTLA4, GITR, and ICOS molecules and up-regulated Blimp-1 and over-produced IL-10. Moreover, CCR6+ Treg cells significantly suppressed cell proliferation. Taken together, it appears that Tr17 cells play a crucial role in the regulation of autoimmune arthritis.

Peer review status:UNDER REVIEW

26 May 2021Submitted to Clinical & Experimental Immunology
01 Jun 2021Assigned to Editor
01 Jun 2021Submission Checks Completed
02 Jun 2021Reviewer(s) Assigned